In this study of the negative cooperativity of the insulin receptor, we find that cytochalasin-sensitive microfilamentous structures appear to modulate the exposure of cell surface insulin receptors, while microtubules do not seem to be involved. In addition, the negative cooperativity of insulin receptors is unaltered under conditions which disrupt microtubules and microfilaments. A theoretical model has been described previously and has been now successfully used for computer simulation of binding systems and for the analysis of experimental binding data by least-square curve fitting. In the study of thermodynamics of the insulin-receptor interaction, the so-called "hydrophobic effect" was studied since hydrophobic reactions have a characteristic dependence on temperature. The analysis of the data indicated that the formation of the insulin-receptor complex is driven by entropy at low temperature and by enthalpy at higher temperatures. These results support the concept that the formation of the insulin-receptor complex is in large part driven by a hydrophobic effect and also provide the first detailed thermodynamic analysis of a hormone-receptor interaction. BIBLIOGRAPHIC REFERENCES: Simon, J., Freychet, P., Rosselin, G., and De Meyts, P.: Enhanced Binding Affinity of Chicken Insulin for Receptors in Rat Liver Membranes and Human Lymphocytes: Relationships to the Kinetic Properties of the Hormone-Receptor Interaction. Endocrinol., 100, 115 - 121, 1977. De Meyts, P., Roth, J., Van Obberghen, E., and Waelbroeck, M.: Hormonal Control of the Affinity of Polypeptide Hormone Receptors by Negative Cooperativity and Dissociation Rate Modulation. Endocrinology, Proceedings of the V International Congress of Endocrinology, Hamburg, 1976, (James, V. H. T., ed.), Excerpta Medica, 1977, pp. 578 - 582, volume 1.